A compound having a heavy hydrogen (deuterium and tritium) is said to be useful in various purposes. For example, a deuterated compound is very useful in elucidation of reaction mechanism and substance metabolism and used widely as a labeled compound. Said compound is also known to be useful as drugs, pesticides, organic EL materials, and the like due to change in stability and property itself by isotope effect thereof. A compound having tritium also is said to be useful as a labeled compound in animal tests and the like to survey absorption, distribution, concentration in blood, excretion, metabolism and the like of drugs, etc. Therefore, research on a compound having a heavy hydrogen (deuterium and tritium) has been increasing also in these fields.
Various methods for obtaining these compounds having a heavy hydrogen have conventionally been used, however, among others, there are many problems to be solved in deuteration technology of a heterocyclic ring, and it was difficult to efficiently and industrially obtain a compound having a deuterated heterocyclic ring.
Conventional technology includes, for example, a method for deuteration of a compound having a heterocyclic ring using heavy water, deuterated hydrochloric acid and mercaptoacetic acid [Tetrahedron Letters, 43 (2002), 2389-2392], a method for deuteration of a compound having a heterocyclic ring under a supercritical condition using supercritical heavy water and deuterated anion (Chemical Society Reviews, 1997, Volume 26, 401-406), and a method for deuteration of a compound having a heterocyclic ring at 100° C. using a palladium catalyst reduced with hydrogen gas in advance (Chem. Commun., 2001, 367-368).
However, a method containing the addition process of an acid to a reaction system is not only impossible to deuterate a compound having a heterocyclic ring labile to decomposition under acidic condition but also has a problem that a complicated purifying procedure is required to isolate a deuterated compound by said method because the reaction liquid is not neutral, even if a compound which does not decompose in acidic condition is used as a substrate.
Further, a method using supercritical heavy water has problems that a compound to be a reaction substrate tends to be easily decomposed due to very high reactivity of the supercritical water, as well as that the reaction itself must be conducted under a severe condition such as supercritical condition.
Furthermore, a method wherein the deuteration reaction is conducted at 100° C. using a palladium catalyst reduced with hydrogen gas in advance and heavy water requires a complicated procedure that the palladium catalyst reduced with hydrogen gas has to be freeze-pumped repeatedly before use for the deuteration reaction.
In view of the above situation, development of a method is needed for deuteration of a compound having a heterocyclic ring efficiently and industrially irrespective of presence and non-presence of a substituent or types thereof.